SNHG12 regulates biological behaviors of ox-LDL-induced HA-VSMCs through upregulation of SPRY2 and NUB1

Background and aims: Human vascular smooth muscle cells (HA-VSMCs) are an important cell type involved in atherosclerosis. Low density lipoprotein (LDL) is a lipoprotein particle that carries cholesterol into peripheral tissue cells, and oxidized modified LDL (ox-LDL) is a well-known inducer of the atherosclerosis-related phenotype switch in VSMCs, leading to the occurrence of atherosclerosis. Accumulating studies have revealed that long non-coding RNAs (lncRNAs) mediate the effect of ox-LDL on the atherosclerosis-related biological activities of HA-VSMCs, including proliferation, migration, and apoptosis. However, the mechanism of small nucleolar RNA host gene 12 (SNHG12) in ox-LDL-induced phenotype switch of VSMCs remains unclear. Thus, this research dug in whether SNHG12 mediated the influence of ox-LDL on HA-VSMCs and the potential mechanism.

Methods: Fundamental experiments and functional assays were performed to measure the function of SNHG12 on HA-VSMCs. Then, mechanism assays and rescue assays were performed to study the regulatory mechanism of SNHG12 in HA-VSMCs.

Results: SNHG12 reversed the influence of ox-LDL treatment in enhancing cell proliferative and migratory abilities and weakening apoptotic ability in HA-VSMCs. SNHG12 was a competitive endogenous RNA (ceRNA) competing with sprouty RTK signaling antagonist 2 (SPRY2) to bind to miR-1301-3p, thus up-regulating SPRY2 expression in ox-LDL-treated HA-VSMCs. Besides, SNHG12 recruited serine and arginine rich splicing factor 1 (SRSF1) to stabilize negative regulator of ubiquitin like proteins 1 (NUB1) expression.

Conclusions: This study illustrated that SNHG12 inhibited cell proliferation, migration and facilitated cell apoptosis in ox-LDL-induced HA-VSMCs by up-regulating SPRY2 and NUB1.